(98c) Effect of ALD and MLD Coating on Wetting and Flow Properties of Micron-Sized Inhalation Pharmaceutical Powders

Authors: 
Zhang, F., Delft University of Technology
La Zara, D., Delft University of Technology
Sun, F., Delft University of Technology
Quayle, M. J., AstraZeneca R&D Gothenburg
Petersson, G., AstraZeneca R&D Gothenburg
Folestad, S., AstraZeneca R&D Gothenburg
van Ommen, J. R., Delft University of Technology
Budesonide powder is an important pharmaceutical ingredient, used to treat asthma or chronic obstructive pulmonary disease by respiratory inhalation. As an important physical property of Budesonide, wettability has a significant influence on dissolution rates and drug release characteristics. Good flowability of Budesonide powders is vital in the re-suspending of powder in inhalers. However, micron-sized Budesonide powders generally exhibit poor flowability as the inter-particle cohesive forces play a dominant role in the bulk powder behavior when the size of individual particles is less than 30 microns.

Coating of powder material can be a solution to modify surface properties of individual particles, so as to improve wettability and flowability. Therefore, we experimentally coated the Budesonide powders (size range of 0.1 to 10 µm) with SiO2, TiO2, Al2O3 and PET (Polyethylene terephthalate) in a vibrated fluidized bed reactor. Nano-sized films of SiO2, TiO2, and Al2O3 was coated on the surface of Budesonide particles via atomic layer deposition (ALD, inorganic coatings). Nano-scaled layers of PET was deposited onto Budesonide via molecular layer deposition (MLD, organic coatings). The effects of different coating materials, coating cycles (thickness) and coating process (ALD and MLD) on the two important properties of Budesonide powders, wettability and flowability were investigated.

Uncoated Budesonide powder is classified as a very hydrophobic material with poor flowability. Improvements both in the wettability and flowability of Budesonide after the ALD coating process are observed. The coated Budesonide becomes less hydrophobic and its flow property improves; the degree of improvement depends on the coating material. The positive effect can be further enhanced by increasing the number of coating cycles. In particular, Budesonide coated with TiO2 shows the largest increase in wettability (smallest water contact angle). In contrast to ALD coated Budesonide, PET coated budesonide via MLD becomes more hydrophobic compared to the uncoated Budesonide.